CA2666275A1 - Composes de cyclopropyl-piperazine en tant qu'inhibiteurs calciques - Google Patents
Composes de cyclopropyl-piperazine en tant qu'inhibiteurs calciques Download PDFInfo
- Publication number
- CA2666275A1 CA2666275A1 CA002666275A CA2666275A CA2666275A1 CA 2666275 A1 CA2666275 A1 CA 2666275A1 CA 002666275 A CA002666275 A CA 002666275A CA 2666275 A CA2666275 A CA 2666275A CA 2666275 A1 CA2666275 A1 CA 2666275A1
- Authority
- CA
- Canada
- Prior art keywords
- carbonyl
- benzhydrylpiperazin
- methanone
- cyclopropyl
- benzhydrylpiperazine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 229940127291 Calcium channel antagonist Drugs 0.000 title description 8
- 239000000480 calcium channel blocker Substances 0.000 title description 5
- HNZJIWIXRPBFAN-UHFFFAOYSA-N 1-cyclopropylpiperazine Chemical class C1CC1N1CCNCC1 HNZJIWIXRPBFAN-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 114
- 230000000694 effects Effects 0.000 claims abstract description 41
- 238000000034 method Methods 0.000 claims abstract description 37
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 34
- 102000003922 Calcium Channels Human genes 0.000 claims abstract description 29
- 108090000312 Calcium Channels Proteins 0.000 claims abstract description 29
- 108090000699 N-Type Calcium Channels Proteins 0.000 claims abstract description 28
- 102000004129 N-Type Calcium Channels Human genes 0.000 claims abstract description 28
- 125000000217 alkyl group Chemical group 0.000 claims description 60
- -1 4-benzhydrylpiperazin-1-yl Chemical group 0.000 claims description 58
- 125000003118 aryl group Chemical group 0.000 claims description 47
- 125000001072 heteroaryl group Chemical group 0.000 claims description 43
- 125000003342 alkenyl group Chemical group 0.000 claims description 36
- 125000000304 alkynyl group Chemical group 0.000 claims description 35
- 208000002193 Pain Diseases 0.000 claims description 34
- 125000001424 substituent group Chemical group 0.000 claims description 34
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 31
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 17
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 125000005843 halogen group Chemical group 0.000 claims description 13
- 125000002947 alkylene group Chemical group 0.000 claims description 12
- AIMMVWOEOZMVMS-UHFFFAOYSA-N cyclopropanecarboxamide Chemical compound NC(=O)C1CC1 AIMMVWOEOZMVMS-UHFFFAOYSA-N 0.000 claims description 11
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 125000004450 alkenylene group Chemical group 0.000 claims description 6
- 125000004419 alkynylene group Chemical group 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 125000004474 heteroalkylene group Chemical group 0.000 claims description 6
- 208000000094 Chronic Pain Diseases 0.000 claims description 5
- 208000035475 disorder Diseases 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- YCVWHUBMWYGIHJ-VXKWHMMOSA-N (1s,2s)-2-(4-benzhydrylpiperazine-1-carbonyl)-n-tert-butylcyclopropane-1-carboxamide Chemical compound CC(C)(C)NC(=O)[C@H]1C[C@@H]1C(=O)N1CCN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 YCVWHUBMWYGIHJ-VXKWHMMOSA-N 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 3
- 208000019022 Mood disease Diseases 0.000 claims description 3
- 208000018737 Parkinson disease Diseases 0.000 claims description 3
- 208000005298 acute pain Diseases 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- 208000030159 metabolic disease Diseases 0.000 claims description 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 206010015037 epilepsy Diseases 0.000 claims description 2
- 230000004112 neuroprotection Effects 0.000 claims description 2
- JEBPMOIOPUXDLO-UHFFFAOYSA-N (4-benzhydrylpiperazin-1-yl)-[2-(3,5-dimethylpiperazine-1-carbonyl)cyclopropyl]methanone Chemical compound C1C(C)NC(C)CN1C(=O)C1C(C(=O)N2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 JEBPMOIOPUXDLO-UHFFFAOYSA-N 0.000 claims 4
- OABKDOJVQNVYRJ-UHFFFAOYSA-N 2-(4-benzhydrylpiperazine-1-carbonyl)-n,n-di(propan-2-yl)cyclopropane-1-carboxamide Chemical compound CC(C)N(C(C)C)C(=O)C1CC1C(=O)N1CCN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 OABKDOJVQNVYRJ-UHFFFAOYSA-N 0.000 claims 4
- USQHUKPFTUODCF-UHFFFAOYSA-N 2-(4-benzhydrylpiperazine-1-carbonyl)-n-(1-phenylethyl)cyclopropane-1-carboxamide Chemical compound C=1C=CC=CC=1C(C)NC(=O)C1CC1C(=O)N(CC1)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 USQHUKPFTUODCF-UHFFFAOYSA-N 0.000 claims 4
- RHFDZOMILMQEGL-UHFFFAOYSA-N 2-(4-benzhydrylpiperazine-1-carbonyl)-n-(4-methylcyclohexyl)cyclopropane-1-carboxamide Chemical compound C1CC(C)CCC1NC(=O)C1C(C(=O)N2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 RHFDZOMILMQEGL-UHFFFAOYSA-N 0.000 claims 4
- GYGZGKWXCYIXSV-UHFFFAOYSA-N 2-(4-benzhydrylpiperazine-1-carbonyl)-n-(4-tert-butylcyclohexyl)cyclopropane-1-carboxamide Chemical compound C1CC(C(C)(C)C)CCC1NC(=O)C1C(C(=O)N2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 GYGZGKWXCYIXSV-UHFFFAOYSA-N 0.000 claims 4
- DWHAMECCEILUEP-UHFFFAOYSA-N [2-(4-benzhydrylpiperazine-1-carbonyl)cyclopropyl]-(4-benzhydrylpiperazin-1-yl)methanone Chemical compound C1CN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CCN1C(=O)C1CC1C(=O)N(CC1)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 DWHAMECCEILUEP-UHFFFAOYSA-N 0.000 claims 4
- DCQQLISVADUZFO-UHFFFAOYSA-N [2-(4-benzhydrylpiperazine-1-carbonyl)cyclopropyl]-(4-phenylpiperazin-1-yl)methanone Chemical compound C1CN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CCN1C(=O)C1CC1C(=O)N(CC1)CCN1C1=CC=CC=C1 DCQQLISVADUZFO-UHFFFAOYSA-N 0.000 claims 4
- PBHNIZORYGSHSH-UHFFFAOYSA-N [2-(4-benzhydrylpiperazine-1-carbonyl)cyclopropyl]-[4-(2-fluorophenyl)piperazin-1-yl]methanone Chemical compound FC1=CC=CC=C1N1CCN(C(=O)C2C(C2)C(=O)N2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 PBHNIZORYGSHSH-UHFFFAOYSA-N 0.000 claims 4
- ZVUJGXQWWZQPPZ-UHFFFAOYSA-N [2-(4-benzhydrylpiperazine-1-carbonyl)cyclopropyl]-[4-(2-methoxyphenyl)piperazin-1-yl]methanone Chemical compound COC1=CC=CC=C1N1CCN(C(=O)C2C(C2)C(=O)N2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 ZVUJGXQWWZQPPZ-UHFFFAOYSA-N 0.000 claims 4
- LOUFQFSCBMOTEG-UHFFFAOYSA-N [2-[(4-benzhydrylpiperazin-1-yl)methyl]cyclopropyl]-(4-methylpiperidin-1-yl)methanone Chemical compound C1CC(C)CCN1C(=O)C1C(CN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 LOUFQFSCBMOTEG-UHFFFAOYSA-N 0.000 claims 4
- ANJRGBZZDMTSLM-UHFFFAOYSA-N [2-(4-benzhydrylpiperazine-1-carbonyl)cyclopropyl]-[4-[(4-methylcyclohexyl)methyl]piperazin-1-yl]methanone Chemical compound C1CC(C)CCC1CN1CCN(C(=O)C2C(C2)C(=O)N2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 ANJRGBZZDMTSLM-UHFFFAOYSA-N 0.000 claims 3
- OABKDOJVQNVYRJ-DQEYMECFSA-N (1s,2s)-2-(4-benzhydrylpiperazine-1-carbonyl)-n,n-di(propan-2-yl)cyclopropane-1-carboxamide Chemical compound CC(C)N(C(C)C)C(=O)[C@H]1C[C@@H]1C(=O)N1CCN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 OABKDOJVQNVYRJ-DQEYMECFSA-N 0.000 claims 2
- FQXUGPOUZMQLET-VXKWHMMOSA-N (1s,2s)-2-(4-benzhydrylpiperazine-1-carbonyl)-n-(2-methoxyethyl)cyclopropane-1-carboxamide Chemical compound COCCNC(=O)[C@H]1C[C@@H]1C(=O)N1CCN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 FQXUGPOUZMQLET-VXKWHMMOSA-N 0.000 claims 2
- BJNKLOUSAHGMRQ-DQEYMECFSA-N (1s,2s)-2-(4-benzhydrylpiperazine-1-carbonyl)-n-(4-fluorophenyl)cyclopropane-1-carboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)[C@@H]1[C@@H](C(=O)N2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 BJNKLOUSAHGMRQ-DQEYMECFSA-N 0.000 claims 2
- RHFDZOMILMQEGL-HWBSZQFVSA-N (1s,2s)-2-(4-benzhydrylpiperazine-1-carbonyl)-n-(4-methylcyclohexyl)cyclopropane-1-carboxamide Chemical compound C1CC(C)CCC1NC(=O)[C@@H]1[C@@H](C(=O)N2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 RHFDZOMILMQEGL-HWBSZQFVSA-N 0.000 claims 2
- GYGZGKWXCYIXSV-PAIGMYNKSA-N (1s,2s)-2-(4-benzhydrylpiperazine-1-carbonyl)-n-(4-tert-butylcyclohexyl)cyclopropane-1-carboxamide Chemical compound C1CC(C(C)(C)C)CCC1NC(=O)[C@@H]1[C@@H](C(=O)N2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 GYGZGKWXCYIXSV-PAIGMYNKSA-N 0.000 claims 2
- KLZAKQVFNWDMRM-UIOOFZCWSA-N (1s,2s)-2-(4-benzhydrylpiperazine-1-carbonyl)-n-(cyclohexylmethyl)cyclopropane-1-carboxamide Chemical compound O=C([C@@H]1[C@H](C1)C(=O)N1CCN(CC1)C(C=1C=CC=CC=1)C=1C=CC=CC=1)NCC1CCCCC1 KLZAKQVFNWDMRM-UIOOFZCWSA-N 0.000 claims 2
- VDGJFGCICKITHH-VXKWHMMOSA-N (1s,2s)-2-(4-benzhydrylpiperazine-1-carbonyl)-n-prop-2-ynylcyclopropane-1-carboxamide Chemical compound C#CCNC(=O)[C@H]1C[C@@H]1C(=O)N1CCN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 VDGJFGCICKITHH-VXKWHMMOSA-N 0.000 claims 2
- RWFTYANPIGGIIF-GOTSBHOMSA-N (1s,2s)-2-(4-benzhydrylpiperazine-1-carbonyl)-n-pyridin-2-ylcyclopropane-1-carboxamide Chemical compound O=C([C@@H]1[C@H](C1)C(=O)N1CCN(CC1)C(C=1C=CC=CC=1)C=1C=CC=CC=1)NC1=CC=CC=N1 RWFTYANPIGGIIF-GOTSBHOMSA-N 0.000 claims 2
- SSSPLGGNQQCJSE-PRQUERMQSA-N (1s,2s)-n-(1-adamantyl)-2-(4-benzhydrylpiperazine-1-carbonyl)cyclopropane-1-carboxamide Chemical compound O=C([C@H]1C[C@@H]1C(NC12CC3CC(CC(C3)C1)C2)=O)N(CC1)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 SSSPLGGNQQCJSE-PRQUERMQSA-N 0.000 claims 2
- JEBPMOIOPUXDLO-WXESENMXSA-N (4-benzhydrylpiperazin-1-yl)-[(1s,2s)-2-(3,5-dimethylpiperazine-1-carbonyl)cyclopropyl]methanone Chemical compound C1C(C)NC(C)CN1C(=O)[C@@H]1[C@@H](C(=O)N2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 JEBPMOIOPUXDLO-WXESENMXSA-N 0.000 claims 2
- NLGDPKSPRPQULR-WUGFHMLASA-N (4-benzhydrylpiperazin-1-yl)-[(1s,2s)-2-(4-tert-butyl-3,5-dimethylpiperazine-1-carbonyl)cyclopropyl]methanone Chemical compound C1C(C)N(C(C)(C)C)C(C)CN1C(=O)[C@@H]1[C@@H](C(=O)N2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 NLGDPKSPRPQULR-WUGFHMLASA-N 0.000 claims 2
- PCNJHOOXSHELDE-GOTSBHOMSA-N (4-benzhydrylpiperazin-1-yl)-[(1s,2s)-2-(morpholine-4-carbonyl)cyclopropyl]methanone Chemical compound O=C([C@H]1C[C@@H]1C(=O)N1CCOCC1)N(CC1)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 PCNJHOOXSHELDE-GOTSBHOMSA-N 0.000 claims 2
- BFTHIBBAYRHLJP-UHFFFAOYSA-N (4-benzhydrylpiperazin-1-yl)-[2-(4-tert-butylpiperazine-1-carbonyl)cyclopropyl]methanone Chemical compound C1CN(C(C)(C)C)CCN1C(=O)C1C(C(=O)N2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 BFTHIBBAYRHLJP-UHFFFAOYSA-N 0.000 claims 2
- PCNJHOOXSHELDE-UHFFFAOYSA-N (4-benzhydrylpiperazin-1-yl)-[2-(morpholine-4-carbonyl)cyclopropyl]methanone Chemical compound C1COCCN1C(=O)C1CC1C(=O)N(CC1)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 PCNJHOOXSHELDE-UHFFFAOYSA-N 0.000 claims 2
- PKRZYVNMMFHUKZ-UHFFFAOYSA-N (4-benzhydrylpiperazin-1-yl)-[2-[(tert-butylamino)methyl]cyclopropyl]methanone Chemical compound CC(C)(C)NCC1CC1C(=O)N1CCN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 PKRZYVNMMFHUKZ-UHFFFAOYSA-N 0.000 claims 2
- ABVQYALJUGEYDI-UHFFFAOYSA-N (4-benzhydrylpiperazin-1-yl)-[2-[2,6-dimethyl-4-[(4-methylcyclohexyl)methyl]piperazine-1-carbonyl]cyclopropyl]methanone Chemical compound C1CC(C)CCC1CN1CC(C)N(C(=O)C2C(C2)C(=O)N2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C(C)C1 ABVQYALJUGEYDI-UHFFFAOYSA-N 0.000 claims 2
- VVDZTIZXVXOVTQ-UHFFFAOYSA-N (4-benzhydrylpiperazin-1-yl)-[2-[[(4-tert-butylcyclohexyl)amino]methyl]cyclopropyl]methanone Chemical compound C1CC(C(C)(C)C)CCC1NCC1C(C(=O)N2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 VVDZTIZXVXOVTQ-UHFFFAOYSA-N 0.000 claims 2
- FVBHCKNLIBQJPX-UHFFFAOYSA-N (4-benzhydrylpiperazin-1-yl)-[2-[[di(propan-2-yl)amino]methyl]cyclopropyl]methanone Chemical compound CC(C)N(C(C)C)CC1CC1C(=O)N1CCN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 FVBHCKNLIBQJPX-UHFFFAOYSA-N 0.000 claims 2
- GQMXZAOOWYWREO-UHFFFAOYSA-N 2-(4-benzhydrylpiperazine-1-carbonyl)-n,n-dimethylcyclopropane-1-carboxamide Chemical compound CN(C)C(=O)C1CC1C(=O)N1CCN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GQMXZAOOWYWREO-UHFFFAOYSA-N 0.000 claims 2
- BJNKLOUSAHGMRQ-UHFFFAOYSA-N 2-(4-benzhydrylpiperazine-1-carbonyl)-n-(4-fluorophenyl)cyclopropane-1-carboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)C1C(C(=O)N2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 BJNKLOUSAHGMRQ-UHFFFAOYSA-N 0.000 claims 2
- BUIJGGVYUXZPQD-UHFFFAOYSA-N 2-(4-benzhydrylpiperazine-1-carbonyl)-n-phenylcyclopropane-1-carboxamide Chemical compound C1C(C(=O)N2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C(=O)NC1=CC=CC=C1 BUIJGGVYUXZPQD-UHFFFAOYSA-N 0.000 claims 2
- YCVWHUBMWYGIHJ-UHFFFAOYSA-N 2-(4-benzhydrylpiperazine-1-carbonyl)-n-tert-butylcyclopropane-1-carboxamide Chemical compound CC(C)(C)NC(=O)C1CC1C(=O)N1CCN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 YCVWHUBMWYGIHJ-UHFFFAOYSA-N 0.000 claims 2
- XVBFEQSLASLFFQ-UHFFFAOYSA-N [2-(4-benzhydrylpiperazine-1-carbonyl)cyclopropyl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1C(C(=O)N2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 XVBFEQSLASLFFQ-UHFFFAOYSA-N 0.000 claims 2
- BSQLTLYMISXNEH-UHFFFAOYSA-N [2-(4-benzhydrylpiperazine-1-carbonyl)cyclopropyl]-[4-(2-methoxyethyl)piperazin-1-yl]methanone Chemical compound C1CN(CCOC)CCN1C(=O)C1C(C(=O)N2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 BSQLTLYMISXNEH-UHFFFAOYSA-N 0.000 claims 2
- YRHUJYZXXOYZHK-UHFFFAOYSA-N [2-(4-benzhydrylpiperazine-1-carbonyl)cyclopropyl]-piperidin-1-ylmethanone Chemical compound C1CCCCN1C(=O)C1CC1C(=O)N(CC1)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 YRHUJYZXXOYZHK-UHFFFAOYSA-N 0.000 claims 2
- ZAUSERPELHHVIG-UHFFFAOYSA-N [2-[(4-benzhydrylpiperazin-1-yl)methyl]cyclopropyl]-(3,5-dimethylpiperazin-1-yl)methanone Chemical compound C1C(C)NC(C)CN1C(=O)C1C(CN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 ZAUSERPELHHVIG-UHFFFAOYSA-N 0.000 claims 2
- YIKPSCVQQHJJAT-UHFFFAOYSA-N [2-[(4-benzhydrylpiperazin-1-yl)methyl]cyclopropyl]-(3-methylpiperidin-1-yl)methanone Chemical compound C1C(C)CCCN1C(=O)C1C(CN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 YIKPSCVQQHJJAT-UHFFFAOYSA-N 0.000 claims 2
- WZKAVFZEXASWJX-UHFFFAOYSA-N [2-[(4-benzhydrylpiperazin-1-yl)methyl]cyclopropyl]-(4-tert-butylpiperazin-1-yl)methanone Chemical compound C1CN(C(C)(C)C)CCN1C(=O)C1C(CN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 WZKAVFZEXASWJX-UHFFFAOYSA-N 0.000 claims 2
- JZVKWFLYJSSCMI-UHFFFAOYSA-N [2-[(4-benzhydrylpiperazin-1-yl)methyl]cyclopropyl]-(4-tert-butylpiperidin-1-yl)methanone Chemical compound C1CC(C(C)(C)C)CCN1C(=O)C1C(CN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 JZVKWFLYJSSCMI-UHFFFAOYSA-N 0.000 claims 2
- XNDDYNFHCGLGPU-UHFFFAOYSA-N [2-[(4-benzhydrylpiperazin-1-yl)methyl]cyclopropyl]-morpholin-4-ylmethanone Chemical compound C1COCCN1C(=O)C1CC1CN(CC1)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 XNDDYNFHCGLGPU-UHFFFAOYSA-N 0.000 claims 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims 1
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- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- NDNDKVCAYGJFSD-UHFFFAOYSA-N [2-(4-benzhydrylpiperazine-1-carbonyl)cyclopropyl]-[4-(2-chlorophenyl)piperazin-1-yl]methanone Chemical compound ClC1=CC=CC=C1N1CCN(C(=O)C2C(C2)C(=O)N2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 NDNDKVCAYGJFSD-UHFFFAOYSA-N 0.000 claims 1
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- 125000004193 piperazinyl group Chemical group 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
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- 238000003786 synthesis reaction Methods 0.000 description 22
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- 230000015572 biosynthetic process Effects 0.000 description 21
- 239000000203 mixture Substances 0.000 description 20
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- 210000004027 cell Anatomy 0.000 description 13
- 241000700159 Rattus Species 0.000 description 12
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Classifications
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- A—HUMAN NECESSITIES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
- C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/16—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with acylated ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/04—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Epidemiology (AREA)
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- Endocrinology (AREA)
- Heart & Thoracic Surgery (AREA)
- Psychology (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US85151506P | 2006-10-13 | 2006-10-13 | |
US60/851,515 | 2006-10-13 | ||
PCT/CA2007/001827 WO2008043183A1 (fr) | 2006-10-13 | 2007-10-12 | Composés de cyclopropyl-pipérazine en tant qu'inhibiteurs calciques |
Publications (1)
Publication Number | Publication Date |
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CA2666275A1 true CA2666275A1 (fr) | 2008-04-17 |
Family
ID=39282381
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CA002666275A Abandoned CA2666275A1 (fr) | 2006-10-13 | 2007-10-12 | Composes de cyclopropyl-piperazine en tant qu'inhibiteurs calciques |
Country Status (4)
Country | Link |
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US (1) | US20100105682A1 (fr) |
EP (1) | EP2074105A4 (fr) |
CA (1) | CA2666275A1 (fr) |
WO (1) | WO2008043183A1 (fr) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2651811A1 (fr) * | 2006-05-11 | 2007-11-22 | Neuromed Pharmaceuticals Ltd. | Methode d'augmentation de la biodisponibilite de composes contenant de la benzhydrylpiperazine |
TW201028421A (en) * | 2009-01-15 | 2010-08-01 | Abbott Lab | Novel benzenesulfonamides as calcium channel blockers |
US8409560B2 (en) | 2011-03-08 | 2013-04-02 | Zalicus Pharmaceuticals Ltd. | Solid dispersion formulations and methods of use thereof |
US8591944B2 (en) | 2011-03-08 | 2013-11-26 | Zalicus Pharmaceuticals Ltd. | Solid dispersion formulations and methods of use thereof |
CN104230935A (zh) * | 2011-04-26 | 2014-12-24 | 辽宁利锋科技开发有限公司 | 含有脂环结构化合物的抗肿瘤作用与应用 |
CN102241678B (zh) * | 2011-04-26 | 2014-10-29 | 辽宁利锋科技开发有限公司 | 含有脂环结构化合物的抗肿瘤作用与应用 |
EP4382518A2 (fr) * | 2016-08-23 | 2024-06-12 | Iowa State University Research Foundation, Inc. | Composés et compositions insectifuges, et procédés associés |
CN108299411B (zh) | 2017-01-13 | 2021-02-05 | 中国人民解放军军事医学科学院毒物药物研究所 | 4,4-二苯基哌啶类化合物或其可药用盐、药物组合物及用途 |
WO2018135659A1 (fr) * | 2017-01-23 | 2018-07-26 | 日本ケミファ株式会社 | Inhibiteur du canal calcique de type t dépendant de la tension |
Family Cites Families (22)
Publication number | Priority date | Publication date | Assignee | Title |
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DE4111861A1 (de) * | 1991-04-11 | 1992-10-15 | Schwabe Willmar Gmbh & Co | Benzopyranone, verfahren zu ihrer herstellung und verwendung |
WO1995015958A1 (fr) * | 1993-12-08 | 1995-06-15 | Alcon Laboratories, Inc. | Composes presentant une puissante activite d'antagonistes du calcium et d'antioxydants et leur utilisation en tant qu'agents cytoprotecteurs |
US5624677A (en) * | 1995-06-13 | 1997-04-29 | Pentech Pharmaceuticals, Inc. | Controlled release of drugs delivered by sublingual or buccal administration |
US6565961B2 (en) * | 1997-03-07 | 2003-05-20 | Koslow Technologies Corporation | Absorbent articles |
WO1999055688A1 (fr) * | 1998-04-27 | 1999-11-04 | Warner-Lambert Company | Amides de diarylalkyle substitues en tant qu'antagonistes de canaux calciques |
US6011035A (en) * | 1998-06-30 | 2000-01-04 | Neuromed Technologies Inc. | Calcium channel blockers |
US20040266784A1 (en) * | 1998-06-30 | 2004-12-30 | Snutch Terrance P. | Calcium channel inhibitors comprising benzhydril spaced from piperazine |
US6492375B2 (en) * | 1998-06-30 | 2002-12-10 | Neuromed Technologies, Inc. | Partially saturated calcium channel blockers |
US6310059B1 (en) * | 1998-06-30 | 2001-10-30 | Neuromed Technologies, Inc. | Fused ring calcium channel blockers |
US20040259866A1 (en) * | 1998-06-30 | 2004-12-23 | Snutch Terrance P. | Calcium channel blockers comprising two benzhydril moieties |
US6387897B1 (en) * | 1998-06-30 | 2002-05-14 | Neuromed Technologies, Inc. | Preferentially substituted calcium channel blockers |
US6943168B2 (en) * | 1998-06-30 | 2005-09-13 | Neuromed Technologies Inc. | Calcium channel inhibitors comprising benzhydril spaced from piperazine |
US20060084660A1 (en) * | 1998-06-30 | 2006-04-20 | Neuromed Technologies Inc. | Calcium channel blockers comprising two benzhydril moieties |
US6951862B2 (en) * | 1998-06-30 | 2005-10-04 | Neuromed Technologies, Inc. | Calcium channel blockers comprising two benzhydril moieties |
US7186726B2 (en) * | 1998-06-30 | 2007-03-06 | Neuromed Pharmaceuticals Ltd. | Preferentially substituted calcium channel blockers |
GB0117577D0 (en) * | 2001-02-16 | 2001-09-12 | Aventis Pharm Prod Inc | Novel heterocyclic substituted carbonyl derivatives and their use as dopamine D receptor ligands |
CA2438264A1 (fr) * | 2001-02-16 | 2002-08-29 | Aventis Pharmaceuticals Inc. | Derives de carbonyle substitues heterocycliques et utilisation de ceux-ci en tant que ligands du recepteur de la dopamine d3 |
US6997397B1 (en) * | 2003-04-08 | 2006-02-14 | Continental Afa Dispensing Company | Trigger sprayer nozzle |
US7423149B2 (en) * | 2003-12-23 | 2008-09-09 | Schering Corporation | Substituted n-aryl amidines as selective D1 dopamine receptor antagonists for the treatment of obesity and CNS disorders |
US20050227999A1 (en) * | 2004-04-09 | 2005-10-13 | Neuromed Technologies Inc. | Diarylamine derivatives as calcium channel blockers |
WO2006024160A1 (fr) * | 2004-08-30 | 2006-03-09 | Neuromed Pharmaceuticals Ltd. | Dérivés de l'urée agissant comme agents bloquant un canal de calcium |
WO2006071035A1 (fr) * | 2004-12-31 | 2006-07-06 | Lg Life Sciences, Ltd. | Nouveaux derives de ([1,3]thiazolo[5,4-b]pyridin-2-yl)-2-carboxamide |
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- 2007-10-12 CA CA002666275A patent/CA2666275A1/fr not_active Abandoned
- 2007-10-12 WO PCT/CA2007/001827 patent/WO2008043183A1/fr active Application Filing
- 2007-10-12 US US12/445,256 patent/US20100105682A1/en not_active Abandoned
- 2007-10-12 EP EP07815978A patent/EP2074105A4/fr not_active Withdrawn
Also Published As
Publication number | Publication date |
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WO2008043183A1 (fr) | 2008-04-17 |
US20100105682A1 (en) | 2010-04-29 |
EP2074105A4 (fr) | 2010-10-06 |
EP2074105A1 (fr) | 2009-07-01 |
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